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Oct. 9, 2012 -- Hormone replacement therapy (HRT) may do more than ease hot flashes and mood swings. A new study suggests that women who start taking hormones during menopause might get some protection against heart disease without seeing increases in other serious risks.

The study, which was published in BMJ, tested a theory called the timing hypothesis.

What’s been less clear is whether hormones might be safer and more beneficial if they are replaced as they naturally start to drop off, around the time of menopause.

Though the results of the new study look promising, experts who were not involved in the research caution that it is not a game-changer.

“This trial is not a trial that’s going to change how we prescribe hormone replacement therapy. This isn’t going to change practice. There are issues about this trial,” says Suzanne Steinbaum, MD, director of Women and Heart Disease at Lenox Hill Hospital in New York City.

But she says the new results are intriguing and should open the door to more research.

“Women who are symptomatic with hot flashes, difficulty sleeping, mood swings, difficulty concentrating, who are recently menopausal, these women actually might benefit from HRT. Not just for symptom relief, but for preventing heart attacks and deaths,” Steinbaum says.

Hormone Replacement for Younger Women

The study randomly split 1,006 healthy women in Denmark into two groups: The first group got HRT; the second group got no treatment. All the women in the study were near menopause and no more than two years away from their last menstrual period.

The study was designed to run for 20 years. But researchers stopped it early -- after 10 years -- when results from the large Women’s Health Initiative (WHI) study a decade ago found that women taking combined hormone therapy had more heart attacks, strokes, dangerous blood clots in the legs and lungs, and breast cancer than women taking placebo pills.

Fearing for the safety of the women in their study, the Danish researchers advised them to stop taking their hormones. But they continued to chart the women’s health for nearly six more years.

In contrast to what happened in the WHI, the Danish women who took HRT were less likely to die over the course of the study or be hospitalized because of a heart attack or heart failure.

There were no meaningful differences in strokes, dangerous blood clots, or cancers between the two groups.

“I think this is a breakthrough in the sense that this is what most doctors in the field have believed is the truth,” says researcher Louise Schierbeck, MD, an endocrinologist at Hvidovre Hospital in Denmark.

“When the results from the WHI came, in 2002, everything was turned upside down,” says Schierbeck, referring to the swift impact of that study, which caused millions of women to stop taking their hormones.

But Schierbeck and others think the results of the WHI have unfairly applied to younger women.

“The main problem with the WHI was that the women were so much older. They were, on average 63 years old when they were included in that study,” she says.

“It doesn’t make sense to treat menopausal symptoms when you are more than 10 years away from menopause. By that time, your entire biology has changed. It’s completely unnatural.”

Last week, U.S. researchers announced preliminary results from the smaller Kronos Early Estrogen Prevention Study, showing that younger women could get relief from some of the worst symptoms of menopause with little short-term risk. That study has only followed women for about four years, so it couldn’t shed light on what might happen to cancer risks or dementia as the women got older.

Findings Come With Caveats

While the new study seems to bolster the timing hypothesis, experts caution that it has some important limitations.

The original intent of the trial was to see if HRT could help with bone health. Questions about cancers, strokes, heart disease risks, and deaths were asked after all the data for the study had already been gathered. That can sometimes skew research results.

Women and their doctors knew whether or not they were taking hormones. That can bias the results.

With just over 1,000 women, the study was relatively small. In contrast, the WHI trials of HRT included more than 27,000 women.

The study was partly funded by drug companies that make HRT and thus have a financial interest in the outcome of the study.

In addition, researchers mixed two different groups of women, those with and without a uterus. That’s important because women who’ve had their uterus surgically removed are prescribed a different kind of HRT than women who still have a uterus. They take estrogen alone.

Many studies, including the WHI, have shown that taking estrogen alone is safer for younger women and may even offer some protection against heart disease and breast cancer, compared to when it is balanced with progesterone. Women who still have their uterus have to take both because using estrogen by itself raises the risk for endometrial cancer.

Mixing both groups of women in the study may have muddied the results, says Rowan T. Chlebowski, MD, PhD, chief of medical oncology at the David Geffen School of Medicine at UCLA.

For women who still had their uterus, the study tested an estrogen-progesterone combination that isn’t commonly used in the U.S., Chlebowski says, so it’s unclear whether the results would apply to women in this country.

“Overall, the number of clinical events was far too small to provide reassurance about the risks of stroke, heart attack, blood clots, or cancer with hormone therapy, and the findings should not be used to support the use of long-term hormone therapy for chronic disease prevention,” says JoAnn E. Manson, MD, DrPH, chief of the division of preventive medicine at Brigham and Women's Hospital in Boston.